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Plasma Lipoprotein Lipase Is Associated with Risk for Future Major Adverse Cardiovascular Events in Patients Following Carotid Endarterectomy

  • Joost M. Mekke
    Affiliations
    Department of Vascular Surgery, Division of Surgical Specialties, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands
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  • Maarten C. Verwer
    Affiliations
    Department of Vascular Surgery, Division of Surgical Specialties, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands
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  • Erik S.G. Stroes
    Affiliations
    Department of Experimental Vascular Medicine, Amsterdam Cardiovascular Sciences, Amsterdam UMC, location AMC, Amsterdam, The Netherlands
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  • Jeffrey Kroon
    Affiliations
    Department of Experimental Vascular Medicine, Amsterdam Cardiovascular Sciences, Amsterdam UMC, location AMC, Amsterdam, The Netherlands
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  • Leo Timmers
    Affiliations
    Department of Cardiology, St. Antonius Hospital Nieuwegein, Nieuwegein, The Netherlands
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  • Gerard Pasterkamp
    Affiliations
    Central Diagnostic Laboratory, Division Laboratories and Pharmacy, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands
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  • Gert J. de Borst
    Affiliations
    Department of Vascular Surgery, Division of Surgical Specialties, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands
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  • Author Footnotes
    1 These authors contributed equally.
    Sander W. van der Laan
    Correspondence
    Corresponding authors: Sander W. van der Laan, Central Diagnostics Laboratory, Division Laboratories, Pharmacy, and Biomedical Genetics, University Medical Center Utrecht, Utrecht University, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands: (Sander W. van der Laan)
    Footnotes
    1 These authors contributed equally.
    Affiliations
    Central Diagnostic Laboratory, Division Laboratories and Pharmacy, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands
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  • Author Footnotes
    1 These authors contributed equally.
    Dominique P.V. de Kleijn
    Correspondence
    Corresponding authors: Dominique P.V. de Kleijn, Department of Vascular Surgery (G.04.129), University Medical Centre Utrecht Heidelberglaan 100, 3584 CX Utrecht, The Netherlands. (Dominique P.V. de Kleijn)
    Footnotes
    1 These authors contributed equally.
    Affiliations
    Department of Vascular Surgery, Division of Surgical Specialties, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands

    Netherlands Heart Institute, Utrecht, The Netherlands
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  • Author Footnotes
    1 These authors contributed equally.
Open AccessPublished:January 25, 2023DOI:https://doi.org/10.1016/j.ejvs.2023.01.035
Plasma Lipoprotein Lipase Is Associated with Risk for Future Major Adverse Cardiovascular Events in Patients Following Carotid Endarterectomy
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      Introduction

      Carotid plaque intraplaque haemorrhage (IPH) is associated with future cardiovascular events. It was hypothesised that plasma proteins associated with carotid plaque IPH are also likely to be associated with major adverse cardiovascular events (MACE) after carotid endarterectomy (CEA).

      Methods

      In pre-operative blood samples from patients undergoing CEA within the Athero-Express biobank, proteins involved in cardiovascular disease were measured using three OLINK proteomics immunoassays. The association of proteins with IPH was analysed using logistic regression analyses. Subsequently, the association of the IPH associated plasma proteins with the three year post-operative risk of MACE (including stroke, myocardial infarction, or cardiovascular death) was analysed.

      Results

      Within the three year follow up, 130 patients (18.9%) out of 688 symptomatic and asymptomatic patients undergoing CEA developed MACE. Six out of 276 plasma proteins were found to be significantly associated with IPH, from which only lipoprotein lipase (LPL) was associated with the post-operative risk of MACE undergoing CEA. Within the 30 day peri-operative period, high plasma LPL was independently associated with an increased risk for MACE (adjusted hazard ratio [HR] per standard deviation [SD] 1.60, 1.10 – 2.30), p = .014). From 30 days up to three years, however, high LPL was associated with a lower risk for MACE (adjusted HR per SD 0.80, 0.65 – 0.99, p = .036).

      Conclusion

      High LPL concentrations were found to be associated with a higher risk for MACE in the first 30 post-operative days but associated with a lower risk MACE in the time period from 30 days to three years, meaning that LPL has different hazards at different time points.

      Keywords

      Article info

      Publication history

      Accepted: January 20, 2023
      Received in revised form: December 27, 2022
      Received: February 23, 2022

      Publication stage

      In Press Accepted Manuscript

      Footnotes

      ☆‬‬‬WHAT THIS PAPER ADDS: Liproprotein lipase (LPL) has been independently associated with primary acute myocardial infarction and coronary artery disease. The current study shows that LPL is also associated with secondary major adverse cardiovascular events. In addition to this, LPL was found to have varying hazard at different time point following carotid endarterectomy (CEA), which has not been described before. Moreover, this study demonstrated that higher LPL levels are associated with a more favourable plaque composition consisting of smaller lipid core and less macrophage burden. LPL is currently of particular interest due to possible new therapy strategies that target LPL activity via angiopoietin-like 3, angiopoietin-like 4, or apolipoprotein C3 (APOC3) to reduce the risk of cardiovascular disease.

      Identification

      DOI: https://doi.org/10.1016/j.ejvs.2023.01.035

      Copyright

      © 2023 The Author(s). Published by Elsevier B.V. on behalf of European Society for Vascular Surgery.

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